SU412165A1 - METHOD FOR OBTAINING CARBOXYPE ACID DERIVATIVES - Google Patents

Description

one

This invention relates to organic chemistry, in particular to methods for synthesizing carboxylic acid derivatives, such as esters, anhydrides and acid chlorides, amides and substituted amides, thiol acids and thioesters, acyl derivatives of alkylsilanes.

The method can be used in the preparation of monomers for the synthesis of polyamides and polyesters, as well as esters, anhydrides and acid chlorides of organic acids, including hard-to-reach dicarboxylic acid monoesters for Kolbe synthesis.

Currently, derivatives of carbonic acids are synthesized by the interaction of an organic or inorganic compound containing a mobile hydrogen atom with the corresponding acylating reagent, which is most often used by carboxylic acids themselves, their anhydrides and acid chlorides.

Anhydrides and mixed anhydrides are usually obtained by reacting carboxylic acids or their salts with acid chlorides or (for simple acids), by direct dehydration in the presence of water-removing substances. For the synthesis of carboxylic anhydrides by reaction. double exchange of a mixture of inorganic acid chloride (PClg or SOClo) with a carboxylic acid or

its salts are boiled for 5-7 hours under reflux. Anhydrides are formed, which are largely contaminated with acid chlorides derived from sulfur or phosphorus.

Direct dehydration of acids with prolonged heating produces anhydrides of some aromatic O-dicarboxylic acids or aliphatic dicarboxylic acids containing 4-5 carbon atoms. Cyclic anhydrides are formed. oxy-dicarboxylic acids are converted into polymeric anhydrides with prolonged heating at 230-250 ° C.

However, the above reactions for the preparation of anhydrides are characterized by a high temperature at which the process is carried out (up to 280 ° C), its duration (several hours), the formation of a complex reaction mixture that contains, in addition to the target anhydride, the starting compounds (inorganic acid chlorides, POCl3, acids) and the occurrence of side reactions, accompanied by the elimination of COa from acid molecules. In addition, it is difficult to obtain monomeric anhydrides of high molecular weight, containing more than 6 carbon atoms of dicarboxylic acids by these methods, since the anhydrides are fully metered. The disadvantage of anhydrides (as acylating agents) is that only half of the acid component is used in the reaction. Carboxylic acid chlorides are synthesized by reacting inorganic acid chlorides, such as PCls, POCU, SOC12, and COS12, with carboxylic acids, their salts or anhydrides in the presence of a catalyst (for example, ZnC). The process is carried out at high temperatures, usually above the boiling point of the acid chloride, by passing gaseous COX through an acid melt or by boiling the acid in the presence of SOCla, PCls or POC. The preparation of dicarboxylic acid chlorides by this method is difficult, since they preliminarily form polyanhydrides; therefore, anhydrides and processes are usually used to synthesize their acid chlorides in the presence of catalysts (such as ZnCb). Chlorides, as n anhydrides, are highly effective acylating agents, however, due to the difficulty of their preparation, they are used only for the synthesis of derivatives that cannot be obtained by other methods. As a rule, all acid chlorides are strong lacrimators. They are unstable when stored and easily hydrolyzed in the presence of traces of moisture to carboxylic acids and HC1. The esters of alcohols and phenols are easily formed by the interaction with them of anhydrides and carboxylic acid chlorides. However, in view of the difficulty of obtaining anhydrides and acid chlorides in industrial production, carboxylic acids are used for this process despite their weak acyliruyush ability. Carboxylic acids are stable, their production is sufficiently developed and mastered, which allows obtaining esters of various structures. Acids react with alcohols to form ester and water. Since the process is reversible, the reaction is carried out with continuous removal of water from the reaction volume and in excess of one of the reactants. However, the esterification reaction proceeds at a noticeable rate only for primary alcohols and monocarboxylic acids. Secondary and tertiary alcohols and polycarboxylic acids react with great difficulty. In most cases, the preparation of tertiary alcohols by this method is impossible, since esterification removes water and produces olefin. To carry out acid esterification, prolonged heating of the reacting compounds (up to several tens of hours) in the presence of strong acids (such as H2SO4, HC1, sulfochlorides, etc.) is necessary, which leads to partial decomposition of alcohols (especially tertiary). Aminylation of amines is possible by such acylating agents as anhydrides, acid chlorides, acids. However, practically only anhydrides and acid chlorides are used. Carboxylic acids, due to their low acylating capacity, are rarely used to produce mainly primary amines, mainly. The process of acylation of amines with anhydrides and chlorohydrides proceeds smoothly at low temperatures with a quantitative yield, but due to the difficulty of obtaining acid chlorides and anhydrides, this method has not found application in industrial practice. Thioacids and thioethers are obtained by reacting HjS and mercaptans with anhydrides and acid chlorides by passing gaseous mercaptans or H2S into solutions of acylating compounds while cooling and boiling in the presence of substances that bind HC1 or water. The reactions run smoothly and quantitatively. The preparation of anhydrides and carboxylic acid chlorides is fraught with difficulties: the need to use high temperatures, the duration of the process, the complex composition of the reaction mixture, which makes it difficult to isolate and obtain the target products in their pure form, the use of highly toxic compounds (phosgene, thionyl chloride, and . e.), the hydrolysability of both the initial acylating agents and the final products is easy. Therefore, industrial technology for the preparation of anhydrides and acid chlorides is mastered only for a small group of compounds, such as acetic anhydride, some anhydrides of aromatic and aliphatic acids, acetyl and benzoyl chloride, which prevents the widespread industrial use of compounds of this class. The preparation of derivatives of alcohols (glycols, phenols, etc.), amines (amides), mercaptans, and the like is mainly associated with the use of chlorohydrides and carboxylic anhydrides as acylating agents. At the same time, difficulties in obtaining the corresponding anhydrides and acid chlorides are transferred to the preparation of esters, amides, thioesters, etc. Acylation with carboxylic acids (despite the simplicity of this process) requires considerable energy and time and can be carried out only with a small group sufficiently reactive compounds (primary alcohols). At the same time, with an increase in the molecular weight of the acid, the rate of acylation decreases. In order to simplify and intensify the process, a method for producing carboxylic acid derivatives of general formula J) o, XR-C or XR-Ct is proposed; -RX K R where R is a saturated, unsaturated or aromatic hydrocarbon radical;

R is the residue of an acid, monohydric or polyhydric alcohol, amine, polyamine, imine, dialkylhydroxysilane, C1 or SH;

X —H, OH, COOH, COOCH,

that is, by acylation of an organic or inorganic compound

where X and R have the indicated meanings,

and the process is conducted at a temperature below 30 ° C. It is advisable to carry out the process in an aprotic solvent medium if solid starting materials are used. When using nitrol acid as an acylating agent, it is desirable to conduct the process in

NOH

f XRCf

WITH

,

If there are two mobile hydrogen atoms in compound 3, then the reaction gives compound 2.

Acyl nitramide penetrants and nitrol acids have several advantages over other acylating agents. These are highly effective acylating agents, resistant to moisture, compared to anhydrides and acid chlorides. The process of acylation with these compounds does not require high temperatures and goes with great speed. By changing the temperature, you can drive it at the desired speed. Acylation with derivatives of nitramide or nitrol acids is not accompanied by side reactions, which allows to obtain high purity acyl derivatives.

The use of nitrol acids and nitramide derivatives as acylating agents makes it possible to significantly simplify and simplify the processes for the preparation of such compounds as acid chlorides, anhydrides, esters of secondary alcohols, substituted amides.

Primary nitro compounds or alicyclic alcohols can be used to prepare nitramide derivatives and nitrol acids. So nitrol acids are easily obtained by simple nitrosation of primary nitro compounds with nitrous acid at 10-30 ° C.

Oxidation of alicyclic alcohols with nitric acid at 15-25 ° C leads to the formation of nitrol acids with a carboxyl group at the other end of the chain.

So by oxidation of cyclohexanol with 65% nitric acid, b-nitro-6-hydroxyiminohexanoic acid is obtained with

ki containing a mobile hydrogen atom of general formula 3

Rh

where R has the indicated meanings

acyl derivatives of nitramide or nitrolic acids of general formula 4 or 5 are used as an acylating agent.

Jsloyi

(f

or XR-C

qHNO,

NO.

the presence of catalytic amounts of an inorganic acid, for example HC1, H2SO4, HsPOi.

Nitrol acids under the action of organic and inorganic acids, amines, alcohols undergo a rearrangement into acyl derivatives of nitramide. General scheme for the production of carboxylic acid derivatives

-ВВН- «ХВ-О -t-N O + HoO

Nhno. R

yield up to 95%. It should be noted that in environments where nitrol acids can undergo rearrangement, for example in liquid acids, amines, alcohols, it is possible to carry out acylation both with nitramide derivatives and with nitrol acids themselves. When carrying out the reaction in an aprotic solvent, when nitrol acids are used for acylation, catalytic amounts of an inorganic acid should be added to the reaction mixture.

Since the acylation reaction with the proposed compounds is accompanied by the release of water, in order to obtain the most pure derivatives, it is advisable to remove it from the reaction zone. A small amount of moisture contained in the reactants does not affect the process.

Example 1. 0.1 mol of b-ntro-6-hydroxyimipohexanoic acid is placed in a dry reaction flask equipped with a reflux condenser. Through a dropping funnel, 150 ml of absolute methanol is poured into the flask and, with stirring, it is slowly heated to 50-55 ° C. At this temperature, the NoO selection starts. The mixture is kept until gas evolution ceases, after which it is boiled for another 30-40 minutes. An excess of methanol is distilled off from the resulting solution, and the residual product is distilled off with 5 mm Hg. Art. Select fraction with t. Kip. 152-160 ° C. Pure mocomethyl adipic acid ester is obtained with a yield of 65% (the reaction with other mono- and polybasic alcohols is carried out under similar conditions). The reaction proceeds according to the scheme

.NOH

LEO (1 (CH2) 4C

NO,

, (J

+ 11Г20 + Н20

Hoo (l ((H2U

OCH-:

Example 2. 0.1 mol of b-nitro-b-hydroxyiminohexanoic acid is dissolved in 150 ml of absolute methanol, about 0.1 mol of sulfuric acid is added and the solution is electrolyzed in a single-chamber electrolyzer with a platinum anode and graphite cathoHOO (((H2) 4 (2}

Example 3. 0.1 mol of the 6-nitro-6-hydroxyiminohexane bottle are dissolved in 200 ml of glacial acetic acid containing 1-2% acetic anhydride. The solution is slowly heated with stirring to 70-80 ° C. After cessation of gaseous products, an excess of acetic acid is distilled off under reduced pressure.

HOO (5 (CH) 4Cf

Hz

NOr HOOC (P2) J Q-C (-t-NpO + H.O Example 4. 0.1 mol of 6-nitro-6-hydroxy-25 iminohexanoic acid is dissolved in absolute dioxane and heated to 35-40 ° C.

NOH

NOO ((CH2) 4C

COOHOOC (CIi) NjO-bH Q Example 5. 0.1 mol of 6-nitro-6-hydroxyiminohexanoic acid is dissolved in absolutized dioxane, the mixture is heated to 35-85-40 ° C. In the heated solution slowly at

+ He SNC

NHW02.

house at a current density of 6.0 a / dmz. The temperature in the electrolyzer is maintained not higher than 30 ° C. After passing the calculated amount of electricity from the electrolyte is distilled

excess methanol. The residue consists of sebacipic dimethyl ester, adipic acid monomethyl ester, and small amounts of adipic acid. The output of dimethyl ester of sebacic acid

60-75%. Reactions goes according to the scheme

+ SNZON

NHNO,

The residue is a white crystalline substance with mp. 137 ° C - is a mixed anhydride of adipic and acetic acids, yield 88%.

Mixed anhydrides of other acids (for example, adipic and acrylic acids) are synthesized by a similar method. Reaction scheme

one

.0

SNSUNKNO. 20

0

+ ti. &

JHN02 30 - ,, 0 Hydrogen sulfide is passed through the heated solution and slowly raise the temperature to 60-70 °. The supply of hydrogen sulfide is stopped after passing through a solution of about 3 mol of hydrogen sulfide per 1 mol of 6-nitro-6-hydroxyiminohexanoic acid. Dioxane is distilled off from the solution to obtain resistant and hydride adipic and hydrogen sulfide acids in a yield of up to 85%. The reaction scheme pour 0.1 mol of hydroquinone dissolved in absolutized dioxane. After adding the hydroquinone solution to the solution, the reaction mixture is slowly heated to HO-120 ° C and kept at this temperature for 20-30 minutes. After distilling off the dioxane, the monoacyl derivative of hydroquinone and adipic acid remains in the cube. The yield of crude product is about 70%. Reaction scheme 0-noos (mon.) S-o

 l

noossssn, Xc (noosssnsds:; + noIJO -NHNO Example 6. In concentrated water 70-80 ° C and maintained at this temperature of hexamethylenimine containing 25-30 minutes. After distillation of water, get

OD mole of hexamethylenimine, at 40-45 ° C to about 0.1 mole of the substituted amide adipine, add 0.1 mole of 6-nitro-6-hydroxyiminoic acid and hexamethylenimine. Scheme

hexanoic acid. The solution is heated to 5 reactions

,,

-NOOSSNg) 4G NoosConG With j + HN- (SNg).

I N0 ГНHNO КООСССНг) 4 С СНг CHjСН

Example .7. 0.05 mol of butylnitrol acid, obtained by nitrosation of n-1 nitrobutane, is dissolved in absolute methanol and refluxed and cooled.

ОЬ1 -

ABOUT

/

4- NaO + HjO

N

CHj CHj C, lt2

com for 1 hour. Then excess methanol is distilled off. Butyl acid methyl ester remains in the cube (yield 60%). Reaction scheme

/

H-CHjOHCHN1CH2) 2 (

(HN02 ..o CCCK2) COOH-f HOOCCCH-JiC-O; -oH N20H-HjO

-SND (CH2) 2C Example 8. 1 g of 6-nitro-6-hydroxyimino-hexanoic acid, dissolved in 15 ml of absolute dioxane, is placed in a reactor and gaseous chlorine is passed //

HEP (CH2) 4

HOOS ((H2) 4 -N, jO-bH- 0

Example 9. OD mole of 6-nitro-6-hydroxyminohexa new, K-acids are placed in a dry flask, purged with dry nitrogen and 0.05 mole of absolutized diethylene glycol is added dropwise. When moving, dissolve 6-nitro-6-hydroxyiminohexanoic acid in diethylene glycol and gently heat to 60 ° C. After

/

 +

the basis

JOH

HC1

-NEP ((H

2) 4

NHNO,

about

Cl

the bulk of the product will react, the mixture is heated to 100-120 ° C and maintained at this temperature for 1 hour. The mixture is extracted with absolutized ether, the extract is evaporated, the resulting product is analyzed. The output of diethylene glycol adipate 92%. The process proceeds according to the scheme of sustained hydrogen, maintaining the temperature in the reactor at 40-50 ° C for 1 hour. Then the solvent is blown off with dry nitrogen. The output of monochlorohydrin adipic acid 46%. Reaction scheme